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Early ECMO Flow Index and Arterial Oxygenation Targets and Outcomes in Adults With Cardiogenic Shock Supported With Venoarterial Extracorporeal Membrane Oxygenation
No full textCardiogenic shock (CS) is a life-threatening syndrome characterized by reduced cardiac output and end-organ hypoperfusion, with in-hospital mortality nearing 50% despite contemporary therapies. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a key rescue strategy in refractory CS, providing temporary circulatory support to restore adequate perfusion. However, its use is associated with a high risk of significant complications, including bleeding, thromboembolism, neurologic injury, and limb ischemia.
ECMO flow index and arterial oxygenation are readily modifiable parameters during VA-ECMO support that may influence outcomes. Although full flows (>2.0–2.2 L/min/m²) are commonly targeted, they may increase left ventricular (LV) afterload, impair myocardial recovery, and reduce pulsatile flow. Conversely, partial flows may preserve native ejection, reduce vascular complications, and minimize the need for LV unloading. Additionally, arterial hyperoxia, driven by high oxygen delivery through the membrane oxygenator, has been associated with adverse outcomes, including increased mortality, possibly due to oxidative stress and arterial vasoconstriction. ECMO flows can contribute to the absolute oxygen exposure through shifts in the aortic mixing zone that may expose vital circulations (e.g. coronary, cerebral) to supraphysiologic oxygen levels.
In this thesis, we leveraged data from the Extracorporeal Life Support Organization (ELSO) Registry to examine two interrelated questions. In the first study, we assessed whether initial ECMO flow index was associated with in-hospital mortality, metrics of perfusion, and major complications. In the second study, we evaluated the interaction between flow index and arterial oxygenation and their impact on outcomes. Together, these analyses aim to inform future strategies for optimizing VA-ECMO support in adults with CS.Graduate Educatio
Polydopamine-ECM Coated Titanium to Promote Cementogenesis on Dental Implants
No full textTitanium dental implants integrate directly with surrounding bone, a phenomenon known as osseointegration. Unlike natural teeth supported by periodontal ligaments (PDL), osseointegrated implants have weaker mechanical barriers against bacterial infiltration, heightened inflammation, reduced blood flow, and limited proprioception. Current methods to regenerate peri-implant ligaments involve costly, invasive, and time-intensive procedures.
Polydopamine (PDA) is a biocompatible polymer known for its excellent adhesive properties. Periodontal ligament fibroblasts (PDLFs) play a pivotal role in periodontal tissue maintenance. Recent evidence suggests fibroblasts can induce a cementogenic phenotype by altering titanium surface topography and depositing cementum-like tissue.
This study investigates PDA's efficacy in immobilizing ECM produced by PDLFs on titanium, hypothesizing enhanced cementogenesis on PDA-coated titanium surfaces. We assessed ECM immobilization efficiency, optimized decellularization protocols to retain ECM, and evaluated PDLF differentiation into a cementogenic phenotype. PDLFs cultured on PDA-coated titanium underwent decellularization after 10 days, followed by recellularization for 14 days. Cell interactions and gene expression were assessed using immunofluorescence microscopy, scanning electron microscopy (SEM), and RT-qPCR.
Results demonstrated increased cell numbers on PDA-coated surfaces without affecting attachment or proliferation. Decellularization effectively removed cellular material, preserving key ECM proteins like Collagen I and CEMP-1. Gene expression analysis revealed significant upregulation of cementogenic markers (CP23, CAP, CEMP1, BSP) and downregulation of osteogenic markers (ALP, SOST), especially prominent on PDA-ECM surfaces.
Our findings support that PDA-ECM-coated titanium surfaces promote cementogenic differentiation of PDLFs, potentially enabling peri-implant cementum-like tissue formation and periodontal ligament regeneration.Prosthodontic
Area-level Socioeconomic Status, Preoperative Comorbidities, Mortality And Malperfusion In Acute Type A Aortic Dissection
No full textDespite advances in surgical and postoperative care, in-hospital mortality from Acute Type A Aortic Dissection (ATAAD) remains as high as 22%. If left untreated, the mortality rate is 1% per hour from the emergence of symptoms with 24% mortality within 24 hours. The risk of death is increased further in patients who develop end-organ malperfusion, particularly cerebral and mesenteric, with mesenteric malperfusion being the second most common cause of death after aortic rupture.
End-organ malperfusion is an independent risk factor for early mortality that occurs in up to 34% of patients with ATAAD, with in-hospital mortality rates reaching 86% if more than two organ systems are involved. Despite the time-sensitive nature of ATAAD, interfacility transfer for stable patients to high-volume centers is a class IIa recommendation in major guidelines because of improved survival.
Identifying the social determinants of health, particularly socioeconomic status (SES), and examining its relationship with interfacility transfer and access to care at high-volume centers may offer insights into the challenges faced by ATAAD patients from lower SES backgrounds – particularly in relation to timely transfers and its relationship to their short- and long-term outcomes. Furthermore, exploring whether the characteristics of patients with ATAAD and end-organ malperfusion differ from patients without end-organ malperfusion could offer valuable insights into the pathophysiology of the complication and its established impact on postoperative outcomes.
To answer these questions, we studied the relationship between area-level SES and in-hospital mortality in patients with ATAAD, as well as the relationship between several demographic and preoperative conditions and the occurrence of end-organ malperfusion. We hypothesized that 1) patients with ATAAD from lower area-level socioeconomic background have worse short-term outcomes compared to patients from higher area-level socioeconomic backgrounds at high-volume centers, and 2) ATAAD patients with end-organ malperfusion differ in demographic and preoperative characteristics from patients without end-organ malperfusion.MMSC
Bhakti Yoga Conference: Grace in an Age of Distraction
No full textJoin us. Step into an extraordinary journey of love, devotion, and wisdom. This online conference series brings together prominent voices to explore the transformative path of Bhakti Yoga—the yoga of love and devotion.
Bhakti Yoga is more than a practice; it's a way of life. It's about cultivating a profound, personal connection with the Divine through love, humility, and selfless service. Open to all cultures and traditions, this universal path invites you to awaken the love within and express it in every facet of your life.
This conference is your opportunity to immerse yourself in the wisdom of sincere practitioners as they address the questions and challenges faced by us all. Expect thought-provoking discussions, actionable insights, and a deeper understanding of how to cultivate Grace in an Age of Distraction, and how to incorporate Bhakti Yoga in your daily life.
https://www.happyjackyoga.com/bhakti-yoga-conferenceAuthor's Origina
Cooperative Multi-Agent Graph Bandits
No full textThis thesis studies multi-agent, sequential decision making under restrictions on consecutive actions by extending the multi-armed bandit (MAB) paradigm, a fundamental online learning framework with widespread applications in healthcare, recommendation systems, dynamic pricing, and generative artificial intelligence. Specifically, we present the multi-agent graph bandit problem in which N cooperative agents navigate a connected graph G with K nodes. At each time step, agents play an action associated with their current location and observe a random reward. The edges of G thus represent restrictions on which actions can be played sequentially. Unlike in the existing multi-agent MAB literature, we define a coupled reward function, with the total reward of the system formulated as a weighted sum of the rewards sampled by individual agents.
To address this novel learning scenario, we present the Multi-G-UCB algorithm, which episodically estimates, transitions to, and samples from the multiset of nodes that give optimal system-wide reward. We bound our algorithm's regret (a traditional performance measure in online learning settings) by O(γ√(NKT log T) + γDNK log T), where T is the time horizon, D the diameter of G, and γ a boundedness parameter associated with the weight functions. Our agent-average regret bound is tighter than that of any single-agent algorithm and, when T is large, our collective regret matches state-of-the-art bounds from related but simpler bandit formulations.
Motivated by challenges introduced in real-world deployments, we generalize our framework to model agent and communication failures and develop a robust implementation of our algorithm, Robust-Multi-G-UCB, that achieves the same asymptotic performance in the robust setting. We empirically demonstrate that our algorithm surpasses several important benchmarks and performs well in a diverse array of challenging problem instances before finally recording a hardware demonstration deploying Robust-Multi-G-UCB in real-time on a swarm of light-sensing TurtleBots.Computer Scienc
Consequences of Neurovascular Coupling Impairment on Cortical Processing and Sensory Encoding
No full textThe brain consumes a remarkable amount of energy, receiving 20% of the total cardiac
output yet comprising only 2% of total body mass. While total cerebral blood volume remains
constant, the cerebrovascular network dynamically matches local blood flow to active neural
populations in a process known as neurovascular coupling (NVC). This feature of the cerebral
vasculature generates a spatial and temporal relationship between neuronal activity and
vasomotion. While NVC is widely accepted to be essential for normal brain function and health,
it remains poorly understood how NVC supports neuronal activation.
I characterized a genetic mouse model of NVC impairment and investigated the
consequences on sensory-evoked cortical activity. Using a combination of histological and
imaging approaches, I demonstrated that NVC could be reliably blunted across cortical areas
through genetic recombination of caveolin-1 in arterial endothelial cells. NVC impairment was
observed within one month of gene deletion, and this phenotype was generalizable across the
somatosensory and visual cortices. Using electrophysiology, I demonstrated that NVC
impairment was associated with increased cortical firing at the population level during sensory
activation. In the primary visual cortex, orientation selectivity was diminished, and neurons
displayed wider tuning curves to distinct sensory cues after NVC was impaired. These functional
changes were not accompanied by observable markers of cellular stress or apoptosis. Finally,
NVC-impaired mice underperformed on behavioral tasks designed to measure cognition.
Together, these data directly link NVC to neuronal function for the first time.
Emerging evidence supports the notion that multiple signaling pathways are likely
integrated to produce robust vasodilation during active neuronal signaling. As such, it is of
interest to develop a range of tools that impair NVC through targeting different pathways. I
investigated a series of mouse models with the aim of screening for additional tools to selectively
impair NVC. This work revealed novel insights on the molecular players underlying NVC and
uncovered pathways through which vascular proteins may affect neuronal circuits at the cortical
level. I also identified several unexplored candidates in vascular cells that could serve as new
research targets for the mechanistic understanding of NVC, and potentially new tools for
manipulating NVC strength. These findings pave the way for new lines of investigation and
advance our understanding of NVC, offering critical insights on its role in brain function.Medical Science
The function and development of the left-right asymmetric duck syrinx
No full textDissertation Advisor: Dr. Cliff Tabin Darcy Mishkind
The function and development of the left-right asymmetric duck syrinx
Abstract
Avian diversity, ranging from the stunning tailfeathers and advanced mimicry of the Lyrebird, to the bright red and varied calls of the Northern Cardinal, to the well camouflaged feathers and booming call of the American Bittern, has always captured the interest of biologists. This work explores another example of these varied and striking vocalizations, that of Anatidae (ducks and their relatives), where males are known to produce courtship whistle vocalizations. Unique to ducks, the avian vocal organ, the syrinx, demonstrates left-right asymmetry, and this left-right asymmetry is only in males. In males, there is a left-sided bulla that has long been hypothesized to be necessary for courtship vocalizations, though this has not been tested previously. Further, our understanding of left-right asymmetric development of organ primordia is limited, and the syrinx is a tissue yet to be examined with modern molecular approaches. Finally, the sexual dimorphism of this trait allows us to ask how pathways that are ordinarily separate, the left-right cascade and estrogen signaling, achieve crosstalk.
First, we explore the possibility that the hollow bulla may be responsible for the whistling vocalizations common to male duck courtship displays. It has been hypothesized that the bulla functions as a Helmholtz resonator, and we began to test this by predicting bulla resonance frequencies in duck species based on measurements of the structure. When predictions are compared to frequencies emphasized in various call types in these species, we see evidence for bulla-influenced vocalizations, in particular in species with clear whistling vocalizations. We also see overlap with our predictions in non-courtship vocalizations as well as in female calls, an observation that should be explored in the context of other vocal tract features that alter vocalization frequencies. We find that bulla size is generally positively correlated with body mass. We conclude that there is support for the hypothesis that the bulla functions as a resonance chamber, in particular emphasizing courtship whistle vocalizations.
Following this work, we investigate the development of the laterally asymmetric duck syrinx. We begin by examining literature that describes a possible mechanism of intra-syrinx inhibition by which the left side inhibits right side growth. Previous work observed that, when sliced in half, the growth of the right half is limited when grown in culture with the left half but grows as large as the left when grown in isolation1. Using ex vivo cultures, we did not observe any changes to right side growth as a result of either the culturing of right halves with left syrinx halves at various ratios or the presence of conditioned media taken from left-side cultures. This indicates an intrinsic developmental mechanism that is independent of any secreted factors produced by the opposing syrinx half.
The next chapter explores how hormonal and left-right signaling interface to direct development of the duck syrinx. We characterize the cellular mechanisms at play and find cell division to be the main driver of early left-right asymmetry. Additionally, PITX2, a member of the canonical left-right asymmetry cascade, is present in the duck syrinx in males and females and we see evidence that left-sided expression in the syrinx is derived in ducks as it is not observed in other bird species examined. Results indicate asymmetric PITX2 expression occurs in two waves, the second of which is in the primordial syrinx. We see evidence that bilaterally-expressed BMP activates the second wave of left-sided PITX2 in the tissue primordium through laterally differentially accessible chromatin. Estrogen signaling is then responsible for establishing a sexually dimorphic developmental plan by activating left-sided ESR1 and reducing cell proliferation in the female syrinx and thus promoting bilaterally symmetric growth. Here, we characterize a novel system of left-right asymmetry at the organ level and how pathway integration can occur.
Overall, this work describes the function and development of the duck syrinx. It adds to the discourse on sound production in birds and the question of how novel instances of left-right asymmetry are patterned.Biology, Molecular and Cellula
Oregon Timber, & Other Stories.
No full textTimber is a protagonist in construction, architecture, land use, and landscape. To engage with it is to inherit a sticky milieu of ecologies, language, and threats. Increased wildfire and housing development, both undeniable companions to Oregon forests, are reorganizing our relationship to these landscapes. So too is our increased hope towards building with more engineered wood products. If we are interested in timber’s continued role in architecture’s future, forestry in Oregon has a story to tell us: the ecosystems from which our materials come from, the social and political networks that make them possible, and the importance of understanding one’s own unique relationship to the world in which we build. These stories offer an invitation into new ways of knowing building material, expanded scales of time, and a regenerative belief in land.
This work is my acceptance to this generous invitation. I use it as my way into the questions designers are ripe to ask: where does this material come from, and what is my relationship to it? Fundamentally inspired by the field of environmental history, the essay collection traverses time and place: tours with mill owners, fire risk maps, Indigenous restoration sites, friends I stay with, my uncle’s memories, my grandfather’s ranch, Smokey Bear, the Columbia River, disappeared marshland, reappearing fire. Tales of grief, love, erosion, and growth weave with us. In reading the land its stories, we explore the politics of which architecture and its materiality are deeply embedded, and also of which we each bring to the table as agents in a real environment.Department of Architectur
A Taxonomy of Climate Change and Health Solutions Pathways: Development Of A Strategic Policy Framework
No full textClimate change is increasingly being recognized as the single most significant threat facing global health. Urgency is now growing globally to address the health impacts of this threat. However, despite this momentum, existing frameworks fail to integrate climate change and health (CC&H) pathways with solutions and targets. This applied research project aimed to bridge this gap and create a solutions-focused policy tool to support global health practice.
Through a literature review and semi-structured interviews with global philanthropic organizations, the research identified key challenges and opportunities. Findings revealed that CC&H pathways can be well articulated but that a comprehensive current understanding of the burden of disease associated with CC&H pathways remains elusive. In addition, a lack of formal CC&H strategies amongst philanthropic organizations exists. Many organizations are grappling with how to define and evaluate their CC&H work while overlooking existing global development agenda goals and targets. Overall, a persistent state of confusion prevails.
Investment into the conditions for CC&H solutions to emerge independently of direct philanthropic support was identified as a major conclusion of this project. Philanthropy must invest both directly in CC&H solutions AND indirectly in the conditions that will enable CC&H innovation to occur. Investments must focus on building an understanding of the current burden of disease from climate change and identifying universally agreed-upon CC&H global goals and objectives, including the use of existing global development agenda goals and targets.
To address the state of confusion, a results-oriented novel taxonomy was developed. The Taxonomy for Climate Change and Health Solutions Pathways categorizes seven key CC&H pathways. The seven pathways are extreme temperature, food insecurity, mental well-being (encompassing forced displacement), poor air quality, water insecurity, pathogens and vectors, and health systems. Each pathway includes a description of climate change drivers, the impact of drivers on individual pathophysiology or social systems that influence health, health outcomes associated with each pathway, relevant adaptation and mitigation solutions, and Sustainable Development Goals (SDGs) targets.
As a tool, the taxonomy facilitates communication, enhances understanding of the impact of climate change on health, and can help foster collaboration amongst organizations and stakeholders. In turn, the tool can enable evidence-informed decision-making and transformative policymaking. It is believed to be the first tool to integrate CC&H pathways, solutions and metrics, thereby filling a critical gap in the literature and policy-making practice.Public Healt
From the lab to the field: studying fish locomotor dynamics using animal-borne dataloggers
No full textUnderstanding the mechanics and efficiencies associated with how animals move is essential to understand links between form and function and ultimately understand where and why animals move. However, most current studies of animal biomechanics are focused on stereotyped behaviors and dominated by small-bodied animals due to logistical constraints of laboratory experiments. Instead of bringing an animal into the lab and recording its movements with a camera, we can directly measure the body movement of animals using small acceleration, angular velocity, and magnetic field data loggers. This method allows us to tag large animals and collect spatio-temporally unbiased estimates of their kinematics in both lab conditions and in the wild. In my dissertation, I identify the problems, solutions, and benefits to using this method and I show how we can expand our knowledge of in situ kinematics that would be impossible to document using traditional methods.
In Chapter 1, I demonstrate that individual dataloggers temporally drift apart from each other at a rate that meaningfully disrupts their use for kinematics. I show that these errors are quantifiable in both the lab and field and how to correct them.
In Chapter 2, I deploy multiple dataloggers on a soft robotic system and three diverse species of fish (an agnathan, an elasmobranch, and a teleost), show the diverse metrics that can be generated using multiple dataloggers during both routine and high performance swimming in near-field conditions, and evaluate these metrics against traditional video data.
In Chapters 3 and 4, I develop a novel multitag package and deploy it on smooth dogfish in the wild. In Chapter 3, I use this dataset to test a previous hypothesis that suggested that the anterior and posterior body regions of sharks oscillate at different frequencies. I observed no evidence of different oscillation frequencies between the head and tail and suggest these previous observations are due to short monitoring periods and small errors in location and frequency estimation.
In Chapter 4, I use this multi datalogger data set to recreate the kinematics of sharks in the wild using five smooth dogfish released into Massachusetts Bay. I use data from three data loggers to measure how different body parts move and demonstrate how movement along the body varies with tailbeat frequency during routine swimming. Additionally, I document maximal performance and unsteady behaviors such as turns and show that unsteady behaviors are a significant part of a wild animal’s behavior that are poorly captured in laboratory studies.
Overall, this dissertation demonstrates that important biomechanical metrics can be calculated in situ from multiple data loggers attached to animals in the field, and opens the door for documentation of new behaviors, in new species. This work advances and directly links the biomechanics, behavior and ecology of animals.Biology, Organismic and Evolutionar